Superoxide radical (O.sub.2.sup.-), generated during both spontaneous and enzyme-catalyzed oxidations, is catalytically scavenged by superoxide dismutases (SODs); which, by so doing, provide an important defense (Beyer et al, Prog. Nucl. Acids Res. 40:221 (1991), Fridovich, J. Biol. Chem. 264:7761 (1989)). O.sub.2.sup.-, if not removed by SOD, can: initiate free radical chain oxidations of low molecular weight reductants (Nishikimi, Arch. Biochem. Biophys. 166:273 (1975), Ballou et al, Biochem. Biophys. Res. Commun. 36:898 (1969), Fridovich et al, J. Biol. Chem. 233:1578 (1958), McCord et al, J. Biol. Chem. 243:5753 (1968), McCord et al, J. Biol. Chem. 244:6056 (1969), McCord et al, J. Biol. Chem. 244:6049 (1969)); inactivate enzymes (Kuo et al, J. Biol. Chem. 262:4724 (1987), Takabatake et al, Chem. Pharm. Bull. 40:1644 (1992), Smyk-Randall et al, Free Rad. Biol. Med. 14:609 (1993), Gardner et al, J. Biol. Chem. 266:1478 (1991), Gardner et al, J. Biol. Chem. 266:1478 (1991), Gardner et al, J. Biol. Chem. 266:19328 (1991), Flint et al, J. Biol. Chem. 268:22369 (1993)); and can give rise to very reactive hydroxyl or alkoxyl radicals through iron- or copper-, catalyzed interactions with HOOH or ROOH (Sutton et al, Free Rad. Biol. Med. 6:53 (1989), Smith et al, Free Rad. Res. Commun. 8:101 (1990), Nakae et al, Arch. Biochem. Biophys. 279:315 (1990), Tushelasvili et al, J. Biol. Chem. 266:6401 (1991), Mello-Filho et al, Mutat. Res. 251:109 (1991), Halliwell et al, FEBS Lett. 307:109 (1992)). O.sub.2.sup.- can also react, at a diffusion-limited rate, with NO; yielding peroxynitrite (Huie et al, Free Rad. Res. Commun. 18:195 (1993)).
It is reasonable, therefore, that O.sub.2.sup.- should be a participant in a variety of physiological and pathological processes. The ability of SOD to ameliorate reperfusion injury (Concannon et al, Microsurgery 12:18 (1991), Triana et al, Circ. Res. 69:731 (1991), Erlansson et al, Free Rad. Biol. Med. 9:59 (1990), Fujita et al, Biochem. Biophys. Res. Commun. 129:191 (1992), Hatori et al, Free Rad. Biol. Med. 13:137)), inflammations (Ward et al, Free Rad. Biol. Med. 5:403 (1988), Parizada et al, Free Rad. Res. Commun. 15:297 (1991), Oyanagui et al, Biochem. Pharmacol. 42:991 (1991)), multiorgan failure (Marzi et al, J. Trauma 35:110 (1993)), brain trauma (Muizeloar, Ann. Emerg. Med. 22:1014 (1993)), and other conditions (Flohe, Mol. Cell. Biochem. 84:123 (1988), Gorecki et al, Free Rad. Res. Commun. 12-13:401-410 (1991)), indicates that this is the case. It is apparent therefore that mimics of SOD activity are useful pharmaceutical agents. The ideal mimic should be active, stable, and specific for its substrate (O.sub.2.sup.-). A number of metal complexes have been reported to catalyze the disputation of O.sub.2.sup.- (see, for example, McLaughlin et al, Inorg. Chem. 32:941 (1993), Tian et al, Biochem. Biophys. Res. Commun. 191:646 (1993), Kitajima et al, Inorg. Chem. 32:1879 (1993), Baudry et al, Biochem. Biophys. Res. Commun. 192:964 (1993)). Even the best of the compounds described to date, however, exhibit only -1% of the activity of SOD, are not stable to EDTA, and/or can catalyze reactions in addition to the disputation of O.sub.2.sup.-.